Incident Parkinson's Disease Research Articles

Association between autoimmune diseases and the risk of incident Parkinson's disease

Association between autoimmune diseases and the risk of incident Parkinson's disease

Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort.

Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD. Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk. In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

Istradefylline/L‐DOPA Parkinson's disease therapy and energy coupling

AbstractBackgroundBoth dopamine and adenosine are physiologically involved in cellular energy metabolism.AimNovel approaches targeting delaying progression strategies for Parkinson's disease (PD) examined the effects of long‐term use of A2AR antagonist/istradefylline (IST) adjunct to L‐DOPA (LD), nutshell IST‐LD, with an expected energy coupling (EC) to attenuate neuronal excitotoxicity.MethodsA single‐center prospective open cohort study was conducted at the Department of Neurology, Okinawa Islands, Japan. The cohort included incident and prevalent PD cases that were non‐randomly assigned to the IST‐LD (n = 90) and LD (n = 157) groups, followed by an open‐label treatment in clinical practice from October 2013 to September 2020. Patients were evaluated using physician‐rated MDS‐UPDRS I/III, and patient‐rated MDS‐NMS using the total score, body weight, and blood biomarkers of EC.ResultsAs the primary clinical outcome, MDS‐UPDRS part III scores showed less worsening in the IST‐LD than in the LD group (1.29 ± 6.0 vs. 5.0 ± 6.5, p < 0.01) and off‐time Hoehn and Yahr stage (0.05 ± 0.49 vs. 0.26 ± 0.54, p < 0.01). As the secondary clinical outcome, the detected mean body weight losses were similar between the two groups; however, the evident linkage of the daily dose of LD and variations in the blood markers of IGF‐I and HKII, which were inferred as LD‐mediated energy demand effects, were partially attenuated by IST.ConclusionIST‐LD plays an essential role in behavioral outputs for patients with PD and might contribute to the interplay of energy‐consuming demands of LD with the attenuation of weight loss and emerging type 2 diabetes mellitus.

Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort.

Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk. To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk. In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking). No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (β (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; β (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association. The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

Geographic Clusters of Incident Parkinson Disease in US Medicare Beneficiaries (P11-3.013)

Geographic Clusters of Incident Parkinson Disease in US Medicare Beneficiaries (P11-3.013)

Social isolation and the risk of Parkinson disease in the UK biobank study

Parkinson disease (PD) has become one of the most rapidly growing causes of disability among the older population and social isolation is a major concern in the PD community. However, the relationship between social isolation and future risk of PD remains unclear. This study included 192,340 participants aged 60 or older who were free of dementia and PD at baseline from the UK Biobank study. Social isolation was measured using a composite score derived from three questions on number in household, frequency of friend/family visits, and leisure/social activities. Incident PD cases were identified through electronic health records. Multivariable-adjusted Cox regression models were used to compute the hazard ratio (HR) and 95% confidence interval (CI). Among the 192,340 participants (mean [standard deviation] age, 64.2 [2.9] years; 103,253 [53.7%] women), 89,075 (46.3%) participants were in the least isolated group and 26,161 (13.6%) were in the most isolated group. Over a median follow-up of 12.5 years, 2048 incident PD cases were documented. Compared to the least isolated group, the multivariable-adjusted HRs (95% CIs) for PD were 1.00 (0.91−1.10) for the moderately isolated group and 1.19 (1.05−1.36) for the most isolated group (P-trend = 0.04). The observed association was independent of the genetic susceptibility to PD and consistent in subgroup analyses. Social isolation was associated with a higher risk of PD regardless of genetic risk. Our findings highlighted the importance of developing screening and intervention strategies for social isolation among older adults to reduce the risk of PD.

Purpose in Life and Its Association to Parkinsonism.

Purpose in life has been associated with diverse health outcomes; however, few studies have examined its associations with progressive motor decline in older adults. We tested if higher purpose would be associated with lower likelihood of incident parkinsonism as well as with lower levels and slower rates of increase in parkinsonian signs. Participants were 2,626 older adults from the Rush Memory and Aging Project and Minority Aging Research Study followed for an average of 7.2 years (standard deviation [SD] = 4.6). Purpose was measured using the purpose in life subscale of the modified Ryff's and Keyes's measure of psychological well-being. Four parkinsonian signs (i.e., parkinsonian gait, rigidity, bradykinesia, and tremor) were assessed using the United Parkinson's Disease Rating Scale. We examined purpose with risk of developing incident parkinsonism using Cox proportional hazards models. We also used linear mixed-effect models to assess the association between purpose and parkinsonian sign trajectories. After including demographics, health conditions, and health behaviors in the model, for a 1-SD increase in purpose, the hazards ratio for incident parkinsonism was 0.88 (95% confidence interval [CI] 0.80, 0.97). A 1-SD increase in purpose was associated with a -0.19 (95% CI -0.24, -0.15) point lower score in the global parkinsonian summary score at baseline but no differences in rate of change were evident. Higher purpose was associated with lower hazards of incident parkinsonism and lower levels of parkinsonian signs at baseline. Associations were seen even after adjustment for a wide range of covariates. Findings suggest higher purpose may contribute to maintenance of healthy physical function among older adults.

Causal association between long-term exposure to air pollution and incident Parkinson’s disease

Epidemiological evidence for long-term air pollution exposure and Parkinson’s disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006–2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD.

Prospective cohort study evaluating the association between influenza vaccination and neurodegenerative diseases

The effect of influenza vaccination (FluVac) on the risk of neurodegenerative diseases has not been well evaluated in prospective populations. We aimed to assess the association between FluVac and the risk of dementia and Parkinson’s disease (PD) in people aged 60 years or older through a prospective population-based cohort from the UK Biobank. A time-varying Cox regression model adjusted for baseline and repeatedly measured covariates was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between influenza vaccination and risk of dementia/PD. We took into account 70,938 participants in the cohort, including 38,328 participants who got vaccinated. During a median follow-up period of 12.2 years, 2087 incident dementia cases occurred, including 281 cases who received FluVac and 1806 cases who were not vaccinated. In addition, 742 incident PD cases occurred, among whom 131 cases received FluVac and 611 PD cases did not receive FluVac. FluVac was associated with reduced dementia risk with an HR of 0.83 (95% CI, 0.72–0.95) but was not associated with PD incidence (HR = 1.07; 95% CI, 0.87–1.32) after controlling baseline and repeatedly measured covariates. Further, among all dementia cases, there were 733 Alzheimer’s disease (AD) (94 vaccinated cases and 639 non-vaccinated cases), 307 vascular dementia (VD) (34 vaccinated cases and 273 non-vaccinated cases), and 1047 cases with other dementias (OD) (153 vaccinated cases and 894 non-vaccinated cases). The HRs for the associations between FluVac and AD, VD, and OD were 0.79 (95% CI, 0.63–1.00), 0.58 (95% CI, 0.39–0.86), and 0.94 (95% CI, 0.78–1.14) respectively. A dose-response relationship was found in the association between FluVac and dementia but not in the association with PD. A major limitation of the study is the low accuracy in the diagnosis of dementia subtypes, namely AD, VD, and OD. However, Results of sensitivity analyses were consistent with the primary analyses. In conclusion, influenza vaccination is significantly associated with a reduced risk of incident dementia but not PD in community-dwelling adults in the UK Biobank population.

Physical activity and sleep pattern in relation to incident Parkinson’s disease: a cohort study

BackgroundHow physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson’s disease (PD) remain unknown.ObjectiveTo prospectively investigate the joint associations of PA and sleep pattern with risk of PD.MethodsIncluded were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (< 600 MET-mins/week), medium (600 to < 3000 MET-mins/week) and high (≥ 3000 MET-mins/week) according to the instructions of the UK Biobank. Healthy sleep traits (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were scored from 0 to 5 and were categorized into “ideal sleep pattern” (≥ 3 sleep scores) and “poor sleep pattern” (0–2 sleep scores). Hazard ratios (HRs) and 95% confidence intervals (CIs) of PD were estimated by Cox proportional hazards models.ResultsDuring a median of 11.8 years of follow-up, 1,966 PD events were identified. The PD risk was lower in participants with high PA (HR = 0.73; 95% CI: 0.64, 0.84), compared to those with low PA; and participants with ideal sleep pattern also had a lower risk of PD (HR = 0.78; 95% CI: 0.69, 0.87), compared to those with poor sleep pattern. When jointly investigating the combined effect, participants with both high PA and ideal sleep pattern had the lowest risk of incident PD (HR = 0.55; 95% CI: 0.44, 0.69), compared to those with low PA and poor sleep pattern; notably, participants with high PA but poor sleep pattern also gained benefit on PD risk reduction (HR = 0.74; 95% CI: 0.55, 0.99).ConclusionsBoth high PA and ideal sleep pattern were independently associated with lower risk of developing PD, and those with both high PA level and ideal sleep pattern had the lowest risk. Our results suggest that improving PA levels and sleep quality may be promising intervention targets for the prevention of PD.

Risk of Common Neurological Disorders in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders. We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model. In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy. Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance.

Association of grip strength and walking pace with the risk of incident Parkinson's disease: a prospective cohort study of 422,531 participants.

Muscle weakness is a prominent feature of Parkinson's disease, but whether the occurrence of this deficit in healthy adults is associated with subsequent PD diagnosis remains unclear. This study sought to examine the relationship between muscle strength, represented by grip strength and walking pace, and the risk of incident PD. A total of 422,531 participants from the UK biobank were included in this study. Longitudinal associations of grip strength and walking pace with the risk of incident PD were investigated by Cox proportional hazard models adjusting for several well-established risk factors. Subgroup and sensitivity analyses were also conducted for further validation. After a median follow-up of 9.23years, 2,118 (0.5%) individuals developed incident PD. For per 5kg increment of absolute grip strength, there was a significant 10.2% reduction in the risk of incident PD (HR = 0.898, 95% CI [0.872-0.924], P < 0.001). Similarly, per 0.05kg/kg increment of relative grip strength was related to a 9.2% reduced risk of incident PD (HR = 0.908, 95% CI [0.887-0.929], P < 0.001). Notably, the associations remained consistent when grip strength was calculated as quintiles. Moreover, participants with a slower walking pace demonstrated an elevated risk of incident PD (HR = 1.231, 95%CI [1.075-1.409], P = 0.003). Subgroup and sensitivity analyses further validated the robustness of the observed associations. Our findings showed a negative association of grip strength and walking pace with the risk of incident PD independent of important confounding factors. These results hold potential implications for the early screening of people at high-risk of PD.

Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson’s disease

Inconsistent findings exist regarding the potential association between polluted air and Parkinson’s disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM2.5, PM10, NO2, and NOx were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO2 and PM10 pollution showed HRs and 95% CIs of 1.247 (1.089–1.427) and 1.201 (1.052–1.373) for PD incidence, respectively. Each 10 μg/m3 increase in NO2 and PM10 yielded elevated HRs and 95% CIs for PD of 1.089 (1.026–1.155) and 1.363 (1.043–1.782), respectively. Individuals with significant genetic and PM10 exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145–3.520). Similarly, those with substantial genetic and NO2 exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912–3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility.

Herpes Zoster and Risk of Incident Parkinson's Disease in US Veterans: A Matched Cohort Study.

Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear. The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs. We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes. Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years (interquartile range [IQR 61.4-75.7]); 94% male; median follow-up 4.2 years [IQR 1.9-6.6]), HZ was not associated with an increased risk of incident PD overall (adjusted HR 0.95, 95% CI 0.90-1.01) or in any sensitivity analyses. We found no evidence that HZ was associated with increased risk of incident PD in this cohort. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Frozen Shoulder and the Risk of Parkinson's Disease: A Danish Registry-Based Cohort Study.

Frozen shoulder may be an early preclinical symptom of Parkinson's disease (PD). To examine PD risk after frozen shoulder diagnosis and to evaluate this disorder as a possible manifestation of parkinsonism preceding the clinical recognition of PD and possible target for screening. Danish population-based medical registries were used to identify patients aged ≥40 years with a first-time frozen shoulder diagnosis (1995-2016). A comparison cohort was randomly selected from the general population matched on age and sex. To address detection bias and the specificity of frozen shoulder diagnosis, we performed a sensitivity analysis, using similar matching criteria to select a cohort of patients with back pain diagnosis. The outcome was incident PD. Cumulative incidences and adjusted hazard ratios (HRs) were estimated with 95% confidence intervals (CIs). We identified 37,041 individuals with frozen shoulder, 370,410 general population comparators, and 111,101 back pain comparators. The cumulative incidence of PD at 0-22 years follow-up was 1.51% in the frozen shoulder cohort, 1.03% in the general population cohort, and 1.32% in the back pain cohort. For frozen shoulder versus general population, adjusted HRs were 1.94 (CI: 1.20-3.13) at 0-1 years and 1.45 (CI: 1.24-1.70) at 0-22 years follow-up. For frozen shoulder versus back pain, adjusted HRs were 0.89 (CI: 0.54-1.46) and 1.01 (CI: 0.84-1.21), respectively. Patients with frozen shoulder had an increased PD risk compared with the general population, although the absolute risks were low. Frozen shoulder might sometimes represent early manifestations of PD. Detection bias probably cannot account for the increased PD risk during the long-term follow-up.

Meaning in life and Parkinson’s disease in the UK Biobank

IntroductionMeaning in life is an aspect of eudaimonic well-being associated with lower dementia risk. This research examines whether this protective association extends to Parkinson’s disease (PD). MethodsParticipants (N = 153,569) from the UK Biobank reported on their meaning in life. Cases of PD were identified through health records. ResultsMeaning in life was associated with a 50 % lower likelihood of prevalent PD (OR = 0.68, 95 % CI = 0.59–0.78). Over the 5-year follow-up, meaning was associated with a 35 % lower risk of incident PD (HR = 0.74, 95 % CI = 0.65–0.83), an association robust to sociodemographic characteristics, depression, history of seeking mental health care, smoking, physical activity, and genetic risk and not moderated by age, sex, education, deprivation, or genetic risk. ConclusionsMeaning in life is associated with lower risk of incident PD, an association independent of other major risk factors and generalizable across sociodemographic groups. Meaning is a promising target of intervention for common neurodegenerative diseases.

Prevalence of Cardiovascular Drugs and Oral Anticoagulant Use among Persons with and without Parkinson's Disease.

Cardio- and cerebrovascular diseases are common among persons with Parkinson's disease (PD), but it is unknown how the prevalence of cardiovascular drug and oral anticoagulant use changes in relation to PD diagnosis. We investigated the prevalence of cardiovascular drug and oral anticoagulant use among persons with and without PD among 17,541 persons who received incident PD diagnosis in 2001-2015 in Finland and their 116,829 matched comparison persons. Prevalence was calculated in 6-month time windows from 5 years before to 5 years after PD diagnosis (index date) and compared to a matched cohort without PD using generalized estimating equations. Persons with PD had higher prevalence of any cardiovascular drugs (unadjusted OR = 1.15; 95% CI: 1.11-1.18) and oral anticoagulants (unadjusted OR = 1.16; 95% CI: 1.11-1.22) before index date than those without PD. After index date, persons with PD had lower prevalence of cardiovascular drugs (0.94; 95% CI: 0.91-0.96), and no difference was observed for oral anticoagulants. Prevalence of any cardiovascular drugs on the index date was 66 and 61% for persons with and without PD, respectively. β-blockers were the most common cardiovascular drugs in both cohorts. Warfarin was the most common oral anticoagulant, but the use of direct oral anticoagulants increased during the last years of follow-up. Orthostatic hypotension and weight loss likely explain the decreased cardiovascular drug use after PD diagnosis. Results with oral anticoagulants may reflect clinical assessment of benefits being larger than risks, despite the risks associated with their use in persons with PD.

Change in life space is associated with cognitive decline and increased risk of incident Alzheimer’s and Parkinson’s disease in older men

AbstractBackgroundLife space measures the range of geospatial movement through one’s environment during daily functioning. Prior studies on the association of life space and cognitive change are mostly cross‐sectional and have mixed results. To clarify this association, we prospectively evaluated change in life space with cognitive decline and incident Alzheimer’s disease (AD) and Parkinson’s disease (PD).MethodWe studied 1,684 men enrolled in a prospective study of aging. We excluded individuals with probable dementia or PD at baseline (Study Year 7). Life space was evaluated with the self‐reported University of Alabama at Birmingham Life Space Assessment at Year 7 and Year 14. The composite life space score ranges from 0 (most restricted) to 120 (least restricted). Incident AD or PD was defined as a self‐reported physician diagnosis or medication use at Year 14. We conducted logistic regression analyses examining change in life space with the odds of our outcomes unadjusted and adjusted for age, clinic site, race, education, living arrangement, vascular risk factors, and depression. We also conducted mixed linear effects models to evaluate the association between change in life space and change in 3MS and Trails B score.ResultOf 1,684 men (mean age 77.1 +/‐ 18.7 SD) in our analytic cohort, 80 (4.8%) developed incident AD and 23 (1.4%) developed PD over 7 years. The mean (SD) life space score at baseline was 92.9 (18.7) and change over 7 years was ‐9.9 (22.3). In the fully adjusted model, each 1 SD decrement in life space was associated with increased odds of AD (OR 1.6, 95% CI 1.3, 2.0) and PD (OR 1.6, 95% CI 1.1, 2.5). For each 1 SD decline in life space, men worsened by 20.6 seconds in their Trails B score and 1.15 points in their 3MS score over 7 years (p&lt;0.001 for both).ConclusionIn this novel longitudinal analysis, decline in life space is associated with cognitive decline and incident AD and PD. Future studies should examine whether decline in life space is a sensitive and practical way to identify older individuals at risk for cognitive dysfunction and neurodegenerative disease.

The impact of gender‐specific survival on the incidence of dementia in Parkinson’s disease ‐ A cohort analysis of Parkinson’s disease patients in German health claims data for the years 2006 to 2017

AbstractBackgroundThe aim of our study is to analyze gender‐specific patterns of Parkinson’s disease dementia (PDD) incidence. In addition, we are investigating the extent to which gender differences in survival after initial Parkinson’s disease (PD) diagnosis influence differences in PDD risk among PD patients.MethodWe used a random sample of German longitudinal health claims data of persons at ages 65 years or older (2006‐2017). We identified incident PD cases who were followed‐up for a PDD diagnosis or death. We computed age‐ and gender‐specific PDD incidence rates, death rates, and cumulative PDD incidence functions with death as competing risk. In addition, we performed Cox regression models and Fine and Gray competing‐risk regression models, considering death as a competing event, to calculate PDD hazard ratios (HR), adjusted for important risk factors such as age at PD onset, PD severity in terms of modified Hoehn&amp;Yahr (HY) scale, comorbidities, and medications.ResultOf 2,195 incident PD cases, 602 people died and 750 people received a dementia diagnosis by the end of 2017. 44% of PD men and 45% of PD women had received a dementia diagnosis, 45% of PD men and 32% of PD women had died, and only 11% of PD men but 23% of PD women had survived without a PDD diagnosis. PDD risk among PD patients differs by gender when controlled for age at onset, severity of PD, comorbidities and medications, with men having a higher PDD risk than women (HR = 1.18, p = 0.029). When accounting for death, men and women do not differ regarding their PDD risk (HR = 1.02, p = 0.770). Gender‐specific analyses showed significant age and severity effects in women (Age: HR = 1.05, p&lt;0.001, HY 0‐2.5: reference, HY 3‐5: HR = 1.46, p = 0.011), but not in men.ConclusionWe found that older age at first PD diagnosis and higher disease severity increase PDD risk, but this association is attenuated for PD men when we consider death as a competing risk. This implies that the most frail PD men die rapidly before receiving a dementia diagnosis, whereas women with PD survive at higher rates than men, regardless of their age at onset and disease severity.

Association of accelerometer-measured physical activity intensity, sedentary time, and exercise time with incident Parkinson’s disease

Evidence regarding the association between physical activity and Parkinson’s disease (PD) risk is generally limited due to the use of self-report questionnaires. We aimed to quantify the separate and combined effects of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time and exercise timing with incident PD. 96,422 participants without prior PD and with usable accelerometer data were included from UK Biobank. Time spent in sedentary activity, LPA, MVPA, and exercise timing were estimated using machine learning models. The study outcome was incident PD. Over a median follow-up duration of 6.8 years, 313 participants developed PD. There was a L-shaped association for LPA and MVPA, and a reversed L-shaped association for sedentary time, with the risk of incident PD (all P for nonlinearity < 0.001). Similar trends were found across three time-windows (morning, midday-afternoon, and evening). Compared with those with both low LPA (<3.89 h/day) and low MVPA (<0.27 h/day), the adjusted HR (95% CI) of PD risk was 0.49 (0.36–0.66), 0.19 (0.36–0.66) and 0.13 (0.09–0.18), respectively, for participants with high MVPA only, high LPA only, and both high LPA and high MVPA. Moreover, participants with both low LPA and high sedentary time (≥9.41 h/day) (adjusted HR, 5.59; 95% CI: 4.10–7.61), and those with both low MVPA and high sedentary time (adjusted HR, 3.93; 95% CI: 2.82–5.49) had the highest risk of incident PD. In conclusion, regardless of exercise timing (morning, midday-afternoon, and evening), there was an inverse association for accelerometer-measured MVPA and LPA, and a positive association for sedentary time, with incident PD.